ME PRESSURE-REGULATION IN HEALTH AND DISEASE: We propose a translational Clinical Research Program that extends our previous work on middle ear pressure regulation from basic studies in animals to the clinical environment. The integrating theme for the Program is middle ear pressure dysregulation as a disease caused by either constitutive or situational factors that increase middle ear gas demand, decrease gas supply or both. Our global hypotheses are: otitis media with effusion, i.e. middle ear inflammation with effusion, and related disease expressions are caused and maintained by middle ear pressure dysregulation and treatments to prevent or resolve those pathologies need to specifically address that etiology. This Clinical Research Program consists of four subprojects supported by three Core units. Subproject 1, "Gas Supply, Demand and Middle Ear Gas Balance" develops new protocols for assessing Eustachian tube function in ears with an intact tympanic membrane, determines if the results of those tests predict the incidence of otitis media and other middle ear complications during a viral upper respiratory tract infection, and measures the rate of gas exchange across the Eustachian tube, middle ear mucosa and tympanic membrane for use in refining existing models of middle ear pressure-regulation. Subproject 2, "Eustachian Tube Growth and Development: Anatomy/Function" describes the changes in middle ear pressure-regulation with age and determines if there are predictive anatomical correlates of pressure dysregulation. Subproject 3, "Middle Ear Pressure Disregulation in Cleft Palate Patients: Form-Function Correlates" develops a functional-anatomical description of middle ear pressure-regulation in cleft palate children and determines if functional markers of disregulation in infancy predict disease prevalence at later ages. Subproject 4, "Middle Ear Pressure Disregulation after Tympanostomy Tube Insertion" defines the changes in pressure-regulation after tympanostomy tube insertion for otitis media with effusion and determines whether those measures predict disease recurrence after TT extrusion. Core A, "Administration/Support" provides direction and integration for the Program, manages the financial aspects of all studies, oversees all matters concerning human rights and provides nursing, data entry and statistical services to all subprojects. Core B, "Testing and Imaging" oversees the construction and servicing of the test instruments, field tests newly developed function testing and imaging protocols and performs the testing required by subprojects 1 through 4. Core C, "Modeling" integrates all aspects of the Program by developing consistent mathematical descriptions of middle ear pressure-regulation, Eustachian tube structure-function and the middle ear response to pressure imbalances for use in interpreting the data from subprojects 1 through 4. Subproject 1 and Cores B and C are horizontally integrated with feedback regarding model accuracy for predicting middle ear pressure dysregulation and its disease expressions. This unique Clinical Research Program will continue our tradition of being the only research center in the United States for the comprehensive and intensive study of: 1) middle ear pressure-regulation, 2) the role of pressure dysregulation in disease pathogenesis, 3) the prognostic capabilities of specific tests with respect to future disease experience, and 4) the treatment of those factors identified as underlying pressure dysregulation.